Diffuse axonal injury (DAI) is one of the most common lesions observed in head trauma and results in significant mortality and morbidity. Current imaging techniques can not accurately assess DAI. Our objective is to develop a laboratory test to measure DAI in traumatic brain injury (TBI) . We have developed a sensitive sandwich ELISA that measures neuron-specific, axonally localized protein release from axons after damage. This protein is a proteolytically cleaved form of microtubule-associated protein tau. Our preliminary Western blot studies how that after TBI, tau is release from the axonal compartment of damaged neurons, is proteolytically cleaved and gains access to cerebrospinal fluid (CSF). Employing our develop cleaved-tau ELISA we demonstrate that in TBI patients CSF cleaved-tau levels are elevated 10,000 fold over control patients. The proposed studies will assess the clinical utility of measuring CSF cleaved -tau levels in TBI patients. CSF cleaved-tau levels will be measured at 24 hour intervals in hospitalized TBI patients. Patient clinical condition will be quantified with the Glasgow Coma Scale and patient outcome with the Glasgow Outcome Scale. DAI will be quantified from initial CT scans employing the Marshal rating system. We will determine whether CSF cleaved-tau levels are elevated in TBI patients (N=40) with respect to five different control groups (N=150). The ability of CSF cleaved -tau levels to predict clinical condition and outcome will be assessed. The correlation between CSF cleaved-tau levels and CT-measured DAI will be determined. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE